Studies are in progress on the conformational changes at the active sites of proteinases when these enzymes interact with oligopeptide substrates or specific inhibitors. These changes are monitored by fluorescence spectroscopy, both by measurement of the excited-state lifetime and polarization of the intrinsic tryptophan fluorescence of the enzymes and by the use of extrinsic probe groups attached to substrates or inhibitors. In recent and current work, special attention has been given to the enzymes papain, pepsin, and several aspartyl proteinases related to pepsin.